Clinical Expertise:

Dr. Pollack is an expert on sarcomas, cancers of the bone and soft tissues. He sees sarcoma patients at the Seattle Cancer Care Alliance (SCCA; a partnership between the Fred Hutch, UW and Seattle Children’s Hospital), the largest tertiary referral center for sarcoma patients in the Northwest and an important resource for patients from Eastern Washington, Alaska, Oregon, Idaho and Hawaii. The SCCA is consistently one of the highest enrolling sites for national sarcoma clinical trials, including trials focused on patients with especially rare sarcoma subtypes.

Research Focus:

Dr. Pollack is developing new ways to enhance a sarcoma patient’s immune response against their cancer, and to thereby improve patient outcomes.

Laboratory Studies

Dr. Pollack’s research is focused on the development of novel immunotherapies for patients with advanced sarcoma, particularly Synovial Sarcoma (SS) and Myxoid/ Round Cell Liposarcoma (MRCL). These are two soft tissue sarcoma subtypes that affect young individuals and have a median survival of approximately 1 year in the advanced setting. His laboratory showed SS and MRCL tumors homogenously express many proteins that can be recognized by immune T cells. Such proteins are also known as antigens. The NY-ESO-1 antigen has several features that make it an especially attractive target for immunotherapy.

Using clinical grade reagents, Pollack’s lab pioneered methods for isolating and expanding NY-ESO-1–specific T cells from the peripheral blood of sarcoma patients and adoptively transferring these cells back to patients to specifically kill NY-ESO-1 expressing tumor cells, sparing normal tissues. He is the Sponsor of an Investigational New Drug (IND) submission to the US Food & Drug Administration (FDA), which approved these methods for use in clinical trials.

To further improve clinical responses, Dr. Pollack is addressing two potential means by which SS and MRCL tumors can evade immune control. These were uncovered in his laboratory studies. Two new clinical trials were specifically designed to reverse the immune evasion mechanisms and enhance clinical efficacy of adoptive, NY-ESO-1 targeting T cell therapy.

Clinical Trials

The SCCA sarcoma group has many studies aimed at improving care for patients with sarcoma.
The following clinical studies are integrated with ongoing work in Dr. Pollack’s lab.

A Trial of Pembrolizumab in Combination with Doxorubicin as Treatment for Patients with Advanced Sarcomas: Doxorubicin is one of the most commonly used chemotherapy drugs, used to stop the proliferation of tumor cells in patients with sarcoma and many other cancers. Cancer cells killed by this drug can also provoke an anti-cancer immune response, but anti-sarcoma responses are weak in many patients. Pembrolizumab is an antibody treatment that can invigorate immune T cells by blocking an immune inhibitory molecule (PD-1). This Phase I/II clinical study is testing whether the doxorubicin plus pembrolizumab combination can improve patient outcomes in patients with sarcoma that is metastatic or cannot be removed by surgery.

A Phase I/II Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma: Trabectedin is a chemotherapy drug that is FDA-approved for the treatment of leiomyosarcoma and liposarcoma. It binds to DNA and acts in part by preventing tumor cell replication; it also kills cells, known as tumor-associated macrophages, which otherwise help tumors evade killing by immune T cells. Avelumab is an antibody treatment that activates immune T cells by blocking the PD-L1 immune inhibitory molecule. This early phase trial is testing the trabectedin plus avelumab combination treatment for patients with leiomyosarcoma or liposarcoma that is metastatic or cannot be removed by surgery.

Pembrolizumab and Neoadjuvant Radiation for Large, High-Grade Soft Tissue Sarcomas:
Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors, but it can also help immune T cells find and kill the other tumor cells. Pembrolizumab is an antibody treatment that can further invigorate anti-tumor T cells by blocking an activation inhibitor. This pilot phase I/II trial is for patients with locally advanced, large and high-grade sarcomas who are planning to undergo surgery. Pre-surgery, they will receive pembrolizumab immunotherapy plus radiation therapy.

Dr. Seth Pollack, an oncologist who specializes in sarcoma, believes immunotherapy has the power to recognize cancer and kill it with relatively little toxicity.

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